Dysfunction of the Blood-brain Barrier in Cerebral Microbleeds: from Bedside to Bench

Wang, Hai‐Ling; Zhang, Chunlin; Qiu, Yue; Chen, An‐Qi; Li, Yanan; Hu, Bo

doi:10.14336/ad.2021.0514

Cited by 26 publications

(28 citation statements)

References 226 publications

(255 reference statements)

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“…To this end, first of all, using the PubMed database [ 69 ], we characterized each of the 42 hippocampal DEGs (of tame versus aggressive rats) identified in this work ( Table 2 ), in terms of how downregulation or upregulation of their orthologous human genes can manifest itself in hypertension, as presented [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ,…”

Section: Resultsmentioning

confidence: 99%

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Oshchepkov

Chadaeva

Kozhemyakina

et al. 2022

IJMS

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Although half of hypertensive patients have hypertensive parents, known hypertension-related human loci identified by genome-wide analysis explain only 3% of hypertension heredity. Therefore, mainstream transcriptome profiling of hypertensive subjects addresses differentially expressed genes (DEGs) specific to gender, age, and comorbidities in accordance with predictive preventive personalized participatory medicine treating patients according to their symptoms, individual lifestyle, and genetic background. Within this mainstream paradigm, here, we determined whether, among the known hypertension-related DEGs that we could find, there is any genome-wide hypertension theranostic molecular marker applicable to everyone, everywhere, anytime. Therefore, we sequenced the hippocampal transcriptome of tame and aggressive rats, corresponding to low and high stress reactivity, an increase of which raises hypertensive risk; we identified stress-reactivity-related rat DEGs and compared them with their known homologous hypertension-related animal DEGs. This yielded significant correlations between stress reactivity-related and hypertension-related fold changes (log2 values) of these DEG homologs. We found principal components, PC1 and PC2, corresponding to a half-difference and half-sum of these log2 values. Using the DEGs of hypertensive versus normotensive patients (as the control), we verified the correlations and principal components. This analysis highlighted downregulation of β-protocadherins and hemoglobin as whole-genome hypertension theranostic molecular markers associated with a wide vascular inner diameter and low blood viscosity, respectively.

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Section: Resultsmentioning

confidence: 99%

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Oshchepkov

Chadaeva

Kozhemyakina

et al. 2022

IJMS

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“…However, the molecular and cellular mechanisms underlying BBB dysfunction associated with CMB development remain unclear. Previous studies on CMB and AD have found that cerebral microbleeds may be a bridge between other important theoretical hypotheses about the pathogenesis of AD, the amyloid cascade hypothesis ( 37 – 40 ). In our cohort, we found a more severe CSVD burden and CMB in the probable AD population defined as positive for 18 F-florbetapir PET.…”

Section: Discussionmentioning

confidence: 99%

Correlation of blood–brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer's disease

Cheng

Dai²,

Wu³

et al. 2023

Front. Neurol.

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BackgroundBlood–brain barrier (BBB) damage is considered an important part of Alzheimer's disease (AD) progression, and cerebral small-vessel disease (CSVD) is commonly associated with AD. However, the relationship between BBB damage, small cerebrovascular lesions, especially cerebral microbleeds (CMBs), and amyloid and tau biomarkers remains controversial. Therefore, our study aimed to further investigate their association in our cohort of patients with AD.MethodsA total of 139 individuals were divided into probable AD (18F-florbetapir PET positive, n = 101) and control group (cognitively normal, n = 38). The levels of cerebrospinal fluid (CSF) and plasma t-tau, p-tau181, Aβ40, Aβ42, and albumin were measured using corresponding commercial assay kits, and the CSF/plasma albumin ratio (Qalb), an indicator of BBB dysfunction, was calculated. CSVD burden and the number of CMBs were defined using magnetic resonance imaging.ResultsPatients with AD had higher Qalb (p = 0.0024), higher numbers of CMBs (p = 0.03), and greater CSVD burden (p < 0.0001). In the AD group, CMBs and CSVD correlated with a higher Qalb (p = 0.03), and the numbers of CMBs negatively correlated with CSF Aβ42 (p = 0.02).ConclusionBlood–brain barrier damage was accompanied by a more severe burden of CSVD, including CMB, in patients with AD.

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“…Cerebral microbleeds (CMBs) are defined as small (< 10 mm), hypointensity, round or oval lesions that can be detected using the T2 * gradient-weighted echo and SWI sequence ( 23 – 25 ), and there is no edema around them ( 26 ). A histopathological examination showed that CMBs were a punctate hemorrhagic focus containing hemosiderin deposits, probably caused by leakage of red blood cells in small cerebral vessels (such as arterioles and capillaries) ( 25 ), caused by blood exosmosis caused by degeneration of small vessels, and the subsequent decomposition of hemoglobin released from red blood cells ( 27 , 28 ). CMBs are related to cerebral hemorrhage, ischemic stroke, dementia, Parkinson's disease, Alzheimer's disease, etc.…”

Section: Discussionmentioning

confidence: 99%

“…CMBs are related to cerebral hemorrhage, ischemic stroke, dementia, Parkinson's disease, Alzheimer's disease, etc. ( 25 , 29 – 33 ) and can also be seen in the injury caused by high altitude hypoxia ( 34 ). In the study by PH Hackett et al ( 14 ), six patients who underwent SWI all showed extensive CMB signs, especially in the corpus callosum and the juxtacortical white matter.…”

Section: Discussionmentioning

confidence: 99%

Study of high-altitude cerebral edema using multimodal imaging

Long

Bao²

2023

Front. Neurol.

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ObjectiveTo analyze the brain imaging features of high-altitude cerebral edema (HACE) using computed tomography (CT) and multi-sequence magnetic resonance imaging (MRI) and to explore its injury characteristics.Materials and methodsWe selected 30 patients with HACE diagnosed between January 2012 to August 2022 as the experimental group and 60 patients with dizziness on traveling from the plain to the plateau or from lower altitude to higher altitude in a short period of time as the control group. We collected general clinical data from the experimental group and classified it according to clinical symptoms. In both groups, we then performed a head CT and multi-sequence MRI (T1WI, T2WI, FLAIR, and DWI). Among them, nine patients with HACE were also scanned using susceptibility-weighted imaging (SWI). Finally, we analyzed the images.ResultsAccording to clinical symptoms, we divided the 30 cases of HACE into 12 mild cases and 18 severe cases. There was no significant difference in sex, age, leukocyte, neutrophil, or glucose content between mild and severe HACE. The sensitivity and specificity of the MRI diagnosis were 100 and 100%, respectively, while the sensitivity and specificity of the CT diagnosis were 23.3 and 100%, respectively. The distribution range of deep and juxtacortical white matter edema was significantly larger in severe HACE than in mild HACE (p < 0.001). The corpus callosum edema distribution range in severe HACE was significantly larger than that in mild HACE (p = 0.001). The ADC value of the splenium of the corpus callosum was significantly lower in severe HACE than in mild HACE (p = 0.049). In mild and severe HACE, the signal intensity of the DWI sequence was significantly higher than that of conventional MRI sequences (T1WI, T2WI, FLAIR) (p = 0.008, p = 0.025, respectively). In severe HACE, seven cases showed bilateral corticospinal tract edema at the thalamic level, and SWI showed cerebral microbleeds (CMBs) in five cases, especially in the corpus callosum.ConclusionsMRI has more advantages than CT in the evaluation of HACE, especially in the DWI sequence. The white matter injury of severe HACE is more severe and extensive, especially in the corpus callosum, and some CMBs and corticospinal tract edema may also appear.

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Dysfunction of the Blood-brain Barrier in Cerebral Microbleeds: from Bedside to Bench

Cited by 26 publications

References 226 publications

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

Correlation of blood–brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer's disease

Study of high-altitude cerebral edema using multimodal imaging

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